New therapies are ever-more successful in fighting blood cancers
Dr. Michael Heinrich is at the forefront of saving patients' lives
Dr. Michael Heinrich stares down cancer cells under a microscope in his lab and researches new drugs and treatments for cancers such as leukemia and lymphoma.
He is a staff physician specializing in hematology and oncology at the Knight Cancer Center at OHSU and the Veterans Administration Hospital who has focused his research for the past 15 years on gastrointestinal stromal tumors and chronic myeloid leukemia.
What were trying to do is were trying to cure cancer, he said. The first step is to convert it from an acute disease with a short survival into a chronic disease that can be managed for years or longer. We dont cure diabetes or high blood pressure, but you can live with them with the appropriate treatment.
We are trying to develop treatments that can control blood diseases for long periods of time and with minimal side effects. This is different from past treatments that featured strong doses of chemotherapy given in intense bursts of treatment. Once we control cancers for long periods of time, we can figure what else we need to do to cure cancers.
Heinrich said that 60 percent of his work is devoted to research, 30 percent to patients and 10 percent to teaching and administrative work.
Why people get blood cancers is not as obvious as the link between smoking and lung cancer, for example, but it may be tied to more urbanized environments, Heinrich said. And exposure to pesticides and Agent Orange leads to more cases of lymphoma and leukemia.
In addition, treatment of cancer with radiation or chemotherapy can sometimes result in the delayed development of a blood cancer such as leukemia.
The risk of blood cancers is also related to age, with higher rates seen among children and adults older than 65 years of age. On average, every four minutes one person is diagnosed with a blood cancer in the United States. That translates into about150,000 new cases per year.
Historically, blood cancers were simply classified as either leukemia (cancer of the blood or bone marrow) or lymphoma (cancer of lymph nodes).
"With modern diagnosis and treatment, we now recognize dozens or maybe a couple hundred forms of blood cancers, each with its own distinctive characteristics, Heinrich said. Each of these forms of blood cancer may require a different specialized form of treatment.
Although blood cancers are less common than lung cancer or breast cancer, certain characteristics of blood cancers have allowed researchers to make more rapid progress in figuring out the types of abnormalities that are associated with these cancers.
We know more about lymphoma and leukemia than solid cancers because it is easy to draw blood and look at it, Heinrich said. You can draw blood at any time, and the cancer cells are traveling in the blood, so they can be isolated and studied.
"In contrast, obtaining malignant cells from solid tumors like lung cancer would require a biopsy or surgery. Even then, we know less about how to grow solid tumors and manipulate them outside the body.
Chemotherapy damages dividing cells, and the theory for decades has been that cancer cells divide faster than normal cells, so they are affected more by chemotherapy. But now doctors are finding that this isnt always the case, and this realization has lead researchers to explore new treatment approaches, according to Heinrich.
One of the newer weapons in the arsenal of cancer treatments is using anti-bodies created in test tubes to recognize and bind to proteins that are over-produced by some cancers. These antibodies help the patients immune system to recognize and attack cancer cells. Compared with chemotherapy, many of these immune treatments have a much lower rate of serious side effects and are suitable for long-term treatment to suppress cancer.
Right now, our limitation is how many antibodies can be developed and against which cancer cell proteins, Heinrich said. Even better, researchers have discovered that chemotherapy plus immunotherapy work even better together.
Another new approach to treatment is to use so-called targeted or precision therapy. With these therapies, only the cells that are malfunctioning are shut down. Blocking these malfunctioning cells with a drug can completely cripple cancer cells but with minimal effects on the rest of the body.
Cells are like complicated corporations, Heinrich said. They have different lines of communication, and precision therapy interrupts the communication. In many cases, cancer gets addicted to something, and that makes it easier to attack. Some leukemias are addicted to certain types of signaling, and we can block the pathway. Regular cells dont use just one pathway.
Blocking specific pathways can produce amazing clinical results. However, a disadvantage of these precision drug treatments is that one drug might only work for a few types of cancers.
Heinrich pointed to the success of Gleevec, which has been called a miracle drug and was initially approved for use by the U.S. Food and Drug Administration in 2001 for the treatment of chronic myeloid leukemia. Dr. Brian Druker, director of the Knight Cancer Institute and one of Heinrichs colleagues there, helped develop Gleevec. Since its initial approval, Gleevec has also been approved for use in patients with several different types of cancer, according to Heinrich.
One of the big advances in the past decade has been an explosion in knowledge about the type of DNA mutations that give rise to cancer. Heinrich used the analogy that if DNA is the library, the chromosomes are the books, and medical researchers measure words and letters in the books to look for misspelled words (mutations). Finding certain mutations can help doctors identify the best treatments for their patients.
Clinical trials of new drugs help expand the range of treatments available. Heinrich noted that 70 percent of kids with cancer are involved in clinical trials while only 5 percent of adults participate.
Clinical trials are usually done in three stages, and the third stage may involve hundreds or thousands of patients, Heinrich said. With Gleevec, we found the right dose in phase one, and subsequent studies led to FDA approval within four years.
Another common type of leukemia is chronic lymphocytic leukemia (CLL), and in mid-August the New England Journal of Medicine reported on a new successful drug used to treat it, ibrutinib. CLL cells are addicted to a certain type of immune system signaling, and that is what ibrutinib targets, Heinrich said.
About his work, Heinrich said, Its exciting to get up every day and go to work. We are seeing the results of our work transform routine cancer care. For example, there are 5,000 cases of CML diagnosed in the U.S. annually, and people used to only live for an average of four years. With new treatments, life expectancy is increasing by decades, so many more people are living with it and adding years to their lives.
In addition, the success of Gleevec has lead to the approval of four other drugs to treat CML. These drugs are helpful in cases where patients have rare but serious Gleevec side effects or when Gleevec does not produce the desired results.
In his lab, which Heinrich calls a generic cancer research lab, different types of cancer cells are grown and tested.
We test theories to see what the cell is addicted to, he said. Why do cells die? Why dont cells die? What makes them resistant to drugs? We try to stay one step ahead of the disease. The next discovery leads to the next treatment. Currently the main limitation to curing cancer is not enough knowledge.
We are getting better at translating lab discoveries into new treatments. These days if we find something in the lab, we can sometimes create a new treatment within a year and get it approved by the FDA within two years. This process used to take decades.
Heinrich is outspoken about the lack of funding for medical research in the U.S.
In the long run, the U.S. will be hurt by the lack of funding, he said. The best and brightest are not getting grants at the start of their careers, and if they leave research for other careers, they never go back. We are losing a whole generation of researchers because of lack of funding.
China has taken the lead in the last 10 years in funding research. We need more knowledge to develop better treatments, but without grants, were not getting that knowledge. Its difficult to raise money these days. People are still getting cancer, and they need to know that these cutbacks are happening. These cutbacks are definitely affecting the ability of researchers to find the next treatment.
Heinrich said that if 100 people apply for research grant, maybe 10 will actually get them. What if the 11th person has a brilliant idea, but it will never be tested because of a lack of funding? he asked. It is not always easy to figure out the best approach to make the next big discovery. Although Gleevec has revolutionized the treatment of certain leukemias, it almost never made it to human studies because reviewers had doubts that this type of approach would work.
In fact, Heinrich is so serious about keeping the revenue for research flowing that he sacrificed some of his vacation time recently to write grant applications.